Dinox BV, Groningen, the Netherlands.
Estetra SRL, an affiliate's company of Mithra Pharmaceuticals, Liège, Belgium.
Contraception. 2021 Jun;103(6):386-393. doi: 10.1016/j.contraception.2021.03.003. Epub 2021 Mar 6.
To evaluate the effects of estetrol 15 mg/drospirenone 3 mg on ovarian function.
Single-center, randomized, open-label, parallel study in healthy young women with proven ovulatory cycles. Participants received either estetrol 15 mg/drospirenone 3 mg (E4/DRSP) (n = 41) or ethinylestradiol 20 µg/drospirenone 3 mg (EE/DRSP) (n = 41) in a 24/4-day regimen for 3 consecutive cycles. Follicular size and endometrial thickness were measured by transvaginal ultrasound every 3 days in cycles 1 and 3. Blood was sampled for hormone analysis. Ovarian function expressed as Hoogland score was based on follicular size, serum estradiol (E2) and progesterone (P) concentrations. Ovulation was defined as a ruptured follicle-like structure >13 mm with serum E2 concentrations >100 pmol/L and serum P concentrations >5 nmol/L. We assessed return of ovulation after treatment cessation, and safety throughout the study.
None of the participants ovulated with E4/DRSP use, while one participant ovulated once and one participant ovulated twice during EE/DRSP treatment. Most participants had a Hoogland score of 1 (no ovarian activity) in cycle 1 (85.0% and 82.9% of participants on E4/DRSP and EE/DRSP, respectively) and in cycle 3 (65.8% and 83.8%, respectively). E4/DRSP suppressed follicle-stimulating hormone and luteinizing hormone to a lesser extent than EE/DRSP, whereas both treatments comparably suppressed E2 and P and endometrial thickness. Return of ovulation occurred, on average, 15.5 days after E4/DRSP treatment discontinuation. E4/DRSP was safe and well-tolerated.
E4 15 mg/DRSP 3 mg results in adequate ovulation inhibition and ovarian function suppression, comparable to a marketed combined oral contraceptive containing EE/DRSP.
Treatment with E4 15 mg/DRSP 3 mg showed complete ovulation inhibition, despite less suppression of follicle-stimulating hormone and luteinizing hormone compared to EE/DRSP. If it becomes commercially available, E4/DRSP, containing a naturally occurring estrogen, should be as effective as EE/DRSP.
评估雌三醇 15 毫克/屈螺酮 3 毫克对卵巢功能的影响。
在有排卵周期的健康年轻女性中进行的单中心、随机、开放标签、平行研究。参与者接受雌三醇 15 毫克/屈螺酮 3 毫克（E4/DRSP）（n=41）或炔雌醇 20μg/屈螺酮 3 毫克（EE/DRSP）（n=41），连续 3 个周期，24/4 天方案。在第 1 周期和第 3 周期中，每 3 天通过阴道超声测量卵泡大小和子宫内膜厚度。采集血液进行激素分析。卵巢功能用卵泡大小、血清雌二醇（E2）和孕酮（P）浓度表示的 Hoogland 评分来评估。排卵定义为血清 E2 浓度>100 pmol/L 和血清 P 浓度>5 nmol/L 时>13mm 的破裂卵泡样结构。我们评估了治疗停止后的排卵恢复情况和整个研究期间的安全性。
E4/DRSP 组无一人排卵，而 EE/DRSP 组有 1 人排卵 1 次，1 人排卵 2 次。第 1 周期（E4/DRSP 和 EE/DRSP 组分别为 85.0%和 82.9%）和第 3 周期（分别为 65.8%和 83.8%），大多数参与者的 Hoogland 评分为 1（无卵巢活动）。E4/DRSP 对卵泡刺激素和黄体生成素的抑制作用小于 EE/DRSP，而两种治疗方法对 E2 和 P 的抑制作用以及子宫内膜厚度均相似。E4/DRSP 治疗停止后，排卵平均在 15.5 天恢复。E4/DRSP 安全且耐受良好。
E4 15 毫克/DRSP 3 毫克可充分抑制排卵和卵巢功能，与含有 EE/DRSP 的市售复方口服避孕药效果相当。
与 EE/DRSP 相比，E4 15 毫克/DRSP 3 毫克的卵泡刺激素和黄体生成素抑制作用较弱，但能完全抑制排卵。如果它商业化，含有天然雌激素的 E4/DRSP 应该与 EE/DRSP 一样有效。
